STIMULATION OF GASTROINTESTINAL MOTILITY BY CISPLATIN IN THE FERRET -ACTIVATION OF AN INTRINSIC CHOLINERGIC MECHANISM DISSOCIATED FROM EMESIS

Motility was recorded from the corpus, antrum and small intestine of t he urethane anaesthetised ferret. The gastrointestinal effects of the highly emetic cytotoxic anticancer agent, cisplatin were investigated following intravenous administration (I 0 mg/kg i. v.). Following inje ction, cisplatin induced a prompt onset (< 2 min) increase in motility (tone and contraction amplitude) in all regions with a duration of < 15 min. Acute vagotomy did not abolish the effect but reduced the peak amplitude in the antrum only. Chronic subdiaphragmatic vagotomy signi ficantly enhanced the cisplatin-induced rise in tone in the corpus, th e contraction amplitude in the antrum and the duration of the response in the duodenum. The stimulatory effect of cisplatin was blocked in a ll regions by atropine but not naloxone or the 5-HT3 receptor antagoni st ondansetron. This study reports a previously undescribed gastrointe stinal motility effect of cisplatin in vivo that is temporally dissoci ated from emesis. It is proposed that the results provide evidence for a neuroactive effect of cisplatin on enteric cholinergic neurones.